The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease

C Goul, R Peruzzo, R Zoncu - Nature Reviews Molecular Cell Biology, 2023 - nature.com
Abstract The Ser/Thr kinase mechanistic target of rapamycin (mTOR) is a central regulator of
cellular metabolism. As part of mTOR complex 1 (mTORC1), mTOR integrates signals such …

Modulators of protein–protein interactions

LG Milroy, TN Grossmann, S Hennig… - Chemical …, 2014 - ACS Publications
Since Hedin's characterization of trypsin and antitrypsin in 1906,(1) arguably the first
account of a regulatory protein–protein interaction (PPI), contemporary understanding of …

Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes

J Liu, JD Farmer Jr, WS Lane, J Friedman, I Weissman… - Cell, 1991 - cell.com
Although the immediate receptors (immunophilins) of the immunosuppressants cyclosporin
A (CsA) and FK506 are distinct, their similar mechanisms of inhibition of cell signaling …

Protein folding in the cell

MJ Gething, J Sambrook - Nature, 1992 - nature.com
In the cell, as in vitro, the final conformation of a protein is determined by its amino-acid
sequence. But whereas some isolated proteins can be denatured and refolded in vitro in the …

Discovering high-affinity ligands for proteins: SAR by NMR

SB Shuker, PJ Hajduk, RP Meadows, SW Fesik - Science, 1996 - science.org
A nuclear magnetic resonance (NMR)-based method is described in which small organic
molecules that bind to proximal subsites of a protein are identified, optimized, and linked …

The mechanism of action of cyclosporin A and FK506

SL Schreiber, GR Crabtree - Immunology today, 1992 - cell.com
CsA and FK506 are powerful suppressors of the immune system, most notably of T cells.
They act at a point in activation that lies between receptor ligation and the transcription of …

Cis− trans isomerization of organic molecules and biomolecules: implications and applications

C Dugave, L Demange - Chemical reviews, 2003 - ACS Publications
Organic molecules as well as metal complexes may exist as several geometric isomers1
which display distinct physical properties and chemical reactivities. A molecule containing …

Structure of the FKBP12-rapamycin complex interacting with binding domain of human FRAP

J Choi, J Chen, SL Schreiber, J Clardy - Science, 1996 - science.org
Rapamycin, a potent immunosuppressive agent, binds two proteins: the FK506-binding
protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP). A crystal structure of …

The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure

HJ Böhm - Journal of computer-aided molecular design, 1994 - Springer
A new simple empirical function has been developed that estimates the free energy of
binding for a given protein-ligand complex of known 3D structure. The function takes into …

Controlling signal transduction with synthetic ligands

DM Spencer, TJ Wandless, SL Schreiber, GR Crabtree - Science, 1993 - science.org
Dimerization and oligomerization are general biological control mechanisms contributing to
the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and …